Pulmonary hypertension (PH) is a generic term for a group of conditions characterized by elevated blood pressure in the arteries of the lungs (pulmonary arteries). In patients with PH, characteristic changes occur within the pulmonary circulation. These changes include thickening of the linings and obstruction of the small pulmonary blood vessels. As a result of these changes, pressure in the pulmonary circulation rises, and resistance in the blood flowing through the vessels increases. This increased resistance puts a strain on the right side of the heart as it must work harder to pump blood to the lungs. This strain can cause the heart to enlarge, leading to eventual heart failure.
PH is defined as persistently elevated mean pulmonary arterial pressure (MPAP)≥25 mmHg at rest. The definitive diagnosis of PH is made by right heart catheterization (see, e.g., Galiè N. et al., Eur. Heart J. 2015, 29) to measure pressure in the pulmonary circulation which is elevated due to sustained vasoconstriction and vascular remodeling. Vasoconstrictors such as serotonin (5-HT), endothelin-1 (ET-1), and thromboxane, activate signaling cascades in the vascular smooth muscle that cause the sustained vasoconstriction. The World Health Organization (WHO) classification of PH includes five groups (McLaughlin V V, et al, Circulation, 2009, 119: 2250-94; Simonneau G, et al, J Am Coll Cardiol. 2009, 54: S43-54). Pulmonary arterial hypertension (PAH) is WHO group 1. PAH is a particularly severe form of PH characterized by narrowing and obstruction of the precapillary pulmonary arteries leading to increased pulmonary vascular resistance, right-sided heart failure, and premature death. PAH mainly affects young and middle-aged women. The other four types of PH are venous, hypoxic, thromboembolic, and miscellaneous PH.